Making a case for mitochondria in hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a well-known manifestation of inherited mitochondrial disease. Still, currently available gene panels do not include mitochondrial genome sequencing. Mitochondrial dysfunction plays a very important role in the pathogenesis of HCM, whether tested positive or negative by the currently available gene panels for HCM. Mitochondrial DNA variations may act as modifiers of disease manifestation in genotype-positive individuals. In genotype-negative individuals, it may be the primary driver of pathogenesis. A recent study has demonstrated that mitochondrial dysfunction is correlated with septal hypertrophy in genotype-negative HCM, which can be amenable to mitochondria-targeted therapy. It is important to consider mitochondrial genome sequencing as part of the genetic evaluation of HCM.

Plain language summary

Hypertrophic cardiomyopathy or ‘thick heart’ is a common heart problem that can lead to abnormal heart rhythm and even heart failure. In older adults, it is often due to high blood pressure that causes the heart to pump against high resistance and hence becoming thick. However, it can occur without high blood pressure, often in young individuals with underlying heart muscle disease. Sometimes, there are many individuals in a family with thick hearts. In these instances, it is likely genetic. The individual may have a faulty gene related to heart muscle function causing the heart to become thick as an adaptation to inefficient heart muscle function. Mitochondria are tiny organelles inside our cells that make energy. When there is mitochondrial damage, heart muscles cannot generate energy efficiently. This can lead to a thick heart as well. Hence, it is important to test mitochondrial genes along with the heart muscle genes to find the cause of thick heart when it is unexplained, or a genetic cause is suspected.

Article highlights

• Mitochondrial dysfunction is an important contributor to the pathogenesis of hypertrophic cardiomyopathy (HCM).

• In patients with mutations in cardiac sarcomere genes, mitochondrial DNA variations could be an important disease modifier.

• Mitochondrial DNA variations could be the underlying etiology of HCM in individuals tested negative by the current gene panels.

• Current cardiomyopathy gene panels do not include mitochondrial genome sequencing.

• Mitochondrial genome sequencing should be part of the genetic testing strategy for HCM.

Keywords: :

• cardiomyopathy
• gene panel
• hypertrophic cardiomyopathy
• mitochondria
• mitochondrial DNA

Author contributions

P Prasun has drafted the initial and subsequent versions of the manuscript and was involved in patient care, laboratory interpretation, and counseling. U Kohli critically revised the manuscript, was involved in patient care, laboratory interpretation, and interpreted the echocardiology findings.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This report is a retrospective clinical observation that does not require ethics committee approval at this institution. A written informed consent for publication in a medical journal has been obtained from the patient.